8054 Inorg. Chem. 2009, 48, 8054–8056
DOI: 10.1021/ic900983v
Water-Soluble Macrocycles Synthesized via the Weak-Link Approach
Michael J. Wiester and Chad A. Mirkin*
Department of Chemistry and the International Institute for Nanotechnology, Northwestern University,
Evanston, Illinois 60208-3113
Received May 19, 2009
We report a general, high-yielding method for the synthesis of
water-soluble complexes, which is based upon the weak-link
approach to supramolecular coordination chemistry. Specifically,
we have utilized oligomeric ethylene glycol functional groups
appended to the aryl groups of the diphenylphosphine moieties
to achieve solubility. Small molecules or halide ions can be used to
expand these complexes into larger, more flexible macrocyclic
structures. The realization of this approach should allow for the
preparation of allosteric biomimetic structures which can be used in
aqueous media.
unusual reactivity is observed.5 For example, the Fujita
group has shown that a cagelike complex in the shape of an
octahedron can accelerate the Diels-Alder cyclization bet-
ween anthracene and N-cyclohexylmaleimide, where the
maleimide reacts at the terminal anthracene ring instead of
the central one, as is typically seen.5a In a second example,
Raymond and co-workers have demonstrated that a reaction
that is normally acid-catalyzed, the hydrolysis of orthofor-
mates, proceeds in the cavity of a tetrahedron-shaped com-
plex in basic solutions.5b It should be noted that both of these
examples use rigid, nonconformationally addressable struc-
tures, and there are relatively few coordination-chemistry-
based synthetic strategies which allow one to construct
molecules that exhibit all of the aforementioned properties.
There are many powerful methods for constructing large
biomimetic systems. Two of the most popular and extensively
developed are the directional-bonding approach2 and the
weak-link approach (WLA).3,6 The former yields large rigid
structures with well-defined cavities, while the latter yields
two types of structures that can be chemically interconverted
through small molecule reactions that occur at metal hinge
sites (Figure 1). Therefore, the WLA allows one to fulfill two
of the requirements for a biomimetic structure in that it yields
complexes that can have tailorable pockets for both stoichio-
metric and catalytic reactions and structures that can be
chemically toggled between active and inactive conforma-
tions, much in the way a natural allosteric system works.
Indeed, this approach has beenused to prepare a vast array of
supramolecular structures, including mimics of single and
multieffector allosteric enzymes, enzyme linked immunosor-
bent assay, and polymerase chain reaction.7 However, thus
far, all structures made by the WLA are only soluble in
For decades, chemists have been attempting to mimic the
sophisticated structures and exquisite reactivity of com-
pounds commonly found in nature. To effectively realize
the properties of such systems, and enzymes in particular,
chemists need high-yielding synthetic strategies that allow
one to construct highly functional molecules (1) with tailor-
ablerecognition andcatalyticproperties, (2) thatare dynamic
and conformationally addressable, and (3) that exhibit solu-
bility in aqueous media.1 Coordination chemistry provides a
platform for synthesizing biomimetic supramolecular struc-
tures, whereby it is possible to assemble structures in a
convergent manner and typically in high yields and with
excellent selectivity.2,3 In this regard, structures that mimic
the reactivity of enzymes have been prepared by a variety of
different researchers.4 Some of these structures are highly
charged and soluble in aqueous media, creating a hydro-
phobic reaction pocket where, in some instances, new or
*To whom correspondence should be addressed. E-mail: chadnano@
northwestern.edu.
(1) (a) Breslow, R. Acc. Chem. Res. 1995, 28, 146–153. (b) Vriezema, D. M.;
Aragones, M. C.; Elemans, J. A. A. W.; Cornelissen, J. J. L. M.; Rowan, A. E.;
Nolte, R. J. M. Chem. Rev. 2005, 105, 1445–1490. (c) Das, S.; Brudvig, G. W.;
Crabtree, R. H. Chem. Commun. 2008, 413–424.
(2) Fujita, M.; Tominaga, M.; Hori, A.; Therrien, B. Acc. Chem. Res.
2005, 38, 369–378.
(5) (a) Yoshizawa, M.; Tamura, M.; Fujita, M. Science 2006, 312, 251–
254. (b) Pluth, M. D.; Bergman, R. G.; Raymond, K. N. Science 2007, 316, 85–
88.
(6) Gianneschi, N. C.; Masar, M. S. III; Mirkin, C. A. Acc. Chem. Res.
2005, 38, 825–837.
(7) (a) Gianneschi, N. C.; Cho, S.-H.; Nguyen, S. T.; Mirkin, C. A.
Angew. Chem., Int. Ed. 2004, 43, 5503–5507. (b) Yoon, H. J.; Heo, J.; Mirkin, C.
A. J. Am. Chem. Soc. 2007, 129, 14182–14183. (c) Oliveri, C. G.; Gianneschi, N.
C.; Nguyen, S. T.; Mirkin, C. A.; Stern, C. L.; Wawrzak, Z.; Pink, M. J. Am.
Chem. Soc. 2006, 128, 16286–16296. (d) Gianneschi, N. C.; Bertin, P. A.;
Nguyen, S. T.; Mirkin, C. A.; Zakharov, L. N.; Rheingold, A. L. J. Am. Chem.
Soc. 2003, 125, 10508–10509. (e) Kuwabara, J.; Stern, C. L.; Mirkin, C. A. J.
Am. Chem. Soc. 2007, 129, 10074–10075. (f) Heo, J.; Mirkin, C. A. Angew.
Chem., Int. Ed. 2006, 45, 941–944.
(3) (a) Holliday, B. J.; Mirkin, C. A. Angew. Chem., Int. Ed. 2001, 40,
2022–2043. (b) Oliveri, C. G.; Ulmann, P. A.; Wiester, M. J.; Mirkin, C. A. Acc.
Chem. Res. 2008, 41, 1618–1629.
(4) (a) Collman, J. P.; Decreau, R. A. Chem. Commun. 2008, 5065–5076.
(b) Que, L.; Tolman, W. B. Nature 2008, 455, 333–340. (c) Hooley, R. J.; Rebek,
J. Jr Chem. Biol. 2009, 16, 255–264. (d) Yoshizawa, M.; Klosterman; Jeremy, K.;
Fujita, M. Angew. Chem., Int. Ed. 2009, 48, 3418–3438. (e) Amijs, C. H. M.; van
Klink, G. P. M.; van Koten, G. Dalton Trans. 2006, 308–327. (f) Wurthner, F.;
You, C.-C.; Saha-Moller, C. R. Chem. Soc. Rev. 2004, 33, 133–146.
r
pubs.acs.org/IC
Published on Web 07/28/2009
2009 American Chemical Society